Cardamonin reduces chemotherapy-enriched breast cancer stem-like cellsin vitroandin vivo

// Deyong Jia 1 , Yuan Tan 1 , Huijuan Liu 1, 2 , Sarah Ooi 1 , Li Li 1 , Kathryn Wright 1 , Steffany Bennett 1 , Christina L. Addison 1, 3 , Lisheng Wang 1, 4, 5 1 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada 2 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China 3 Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada 4 Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada 5 Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada Correspondence to: Lisheng Wang, e-mail: lwang@uottawa.ca Keywords: chemotherapy, cardamonin, breast cancer stem cells, in vivo Received: April 24, 2015      Accepted: October 06, 2015      Published: October 17, 2015 ABSTRACT The failure of cytotoxic chemotherapy in breast cancers has been closely associated with the presence of drug resistant cancer stem cells (CSCs). Thus, screening for small molecules that selectively inhibit growth of CSCs may offer great promise for cancer control, particularly in combination with chemotherapy. In this report, we provide the first demonstration that cardamonin, a small molecule, selectively inhibits breast CSCs that have been enriched by chemotherapeutic drugs. In addition, cardamonin also sufficiently prevents the enrichment of CSCs when simultaneously used with chemotherapeutic drugs. Specifically, cardamonin effectively abolishes chemotherapeutic drug-induced up-regulation of IL-6, IL-8 and MCP-1 and activation of NF-κB/IKBα and Stat3. Furthermore, in a xenograft mouse model, co-administration of cardamonin and the chemotherapeutic drug doxorubicin significantly retards tumor growth and simultaneously decreases CSC pools in vivo . Since cardamonin has been found in some herbs, this work suggests a potential new approach for the effective treatment of breast CSCs by administration of cardamonin either concurrent with or after chemotherapeutic drugs.